Immunotherapy in Combination With Prednisone and Sirolimus for Kidney Transplant Recipients With Unresectable or Metastatic Skin Cancer
A Phase 2 Study of Nivolumab and Ipilimumab in Combination With Sirolimus and Prednisone in Kidney Transplant Recipients With Selected Unresectable or Metastatic Cutaneous Cancers
4 other identifiers
interventional
16
1 country
26
Brief Summary
This phase II trial tests the combination of nivolumab and ipilimumab with sirolimus and prednisone for the treatment of skin (cutaneous) cancer that cannot be removed by surgery (unresectable) or that has spread from where it first started to other places in the body (metastatic) in kidney transplant recipients. Immunotherapy with nivolumab and ipilimumab, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Sirolimus and prednisone are immunosuppressants that are given to keep the body from rejecting the transplanted kidney. Giving nivolumab and ipilimumab in combination with sirolimus and prednisone may kill more cancer cells, while also keeping the transplanted kidney healthy, in patients with unresectable or metastatic cutaneous cancer who have received a kidney transplant.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1
Started Jul 2024
Typical duration for phase_1
26 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 8, 2023
CompletedFirst Posted
Study publicly available on registry
June 9, 2023
CompletedStudy Start
First participant enrolled
July 24, 2024
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 31, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
January 31, 2027
May 1, 2026
February 1, 2026
2.5 years
June 8, 2023
April 30, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
Disease control without allograft loss
Defined as complete or partial response (CR; PR) or stable disease (SD), at 14 weeks per response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1. The percent of kidney transplant recipients who experience CR/PR/SD at 14 weeks and do not experience allograft loss after administration of nivolumab, ipilimumab, sirolimus, and prednisone will be calculated, along with the corresponding exact 95% confidence interval (CI).
At 14 weeks
Secondary Outcomes (5)
Objective response rate (ORR)
Up to 5 years
Rate of allograft loss and rejection
Up to 5 years
Duration of response (DOR) among patients who experience CR or PR
From the time criteria are met for CR/PR (whichever is first recorded) until the first date that recurrent disease or PD is documented, up to 5 years
Progression-free survival (PFS)
From the first dose of nivolumab + ipilimumab to the date of the first documented tumor progression or death due to any cause, whichever occurs first, up to 5 years
Overall survival
From the first dose of nivolumab + ipilimumab to the date of death from any cause, up to 5 years
Study Arms (1)
Treatment (nivolumab and ipilimumab)
EXPERIMENTALSee detailed description
Interventions
Undergo tumor biopsy
Undergo blood sample collection
Given IV
Undergo kidney biopsy
Undergo MRI
Given IV
Given PO
Given PO
Undergo CT scan
Eligibility Criteria
You may qualify if:
- Patients must be kidney transplant recipients with a functioning allograft who do not currently require dialysis
- Patient's age must be \>= 18 years. Because no dosing or adverse event (AE) data are currently available on the use of nivolumab and ipilimumab in kidney transplant recipients \<18 years of age, children are excluded from this study, but may be eligible for future pediatric trials
- Patients must have histologically or cytologically confirmed non-uveal melanoma, basal cell carcinoma, Merkel cell carcinoma, or cutaneous squamous cell carcinoma for which standard non-immunological medical, surgical, or radiation therapy would be insufficient (i.e., patients who are not surgical candidates). Patients with cutaneous squamous cell carcinoma or Merkel cell carcinoma may enroll without prior medical therapy (e.g., cetuximab or chemotherapy respectively). Non-immunologic standard therapies that patients must have received, refused or for which patients were ineligible include:
- For patients with BRAF-mutant melanoma, prior therapies include BRAF/MEK inhibitors
- For patients with Basal cell carcinoma, prior therapies include hedgehog pathway inhibitors
- Patients must have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria, i.e., at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as \>= 20 mm by chest x-ray or as \>= 10 mm with CT scan, magnetic resonance imaging (MRI), or calipers by clinical exam is preferred, but not required
- Patients must have Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%) performance status criteria
- Leukocytes \>= 2,000/mcL
- Absolute neutrophil count \>= 1,500/mcL
- Platelets \>= 50,000/mcL
- Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN)
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) =\< 2.5 x institutional ULN
- Serum creatinine =\< 3 x ULN
- dd-cfDNA =\< 1.0% and =\< 61% increase
- The effects of nivolumab and ipilimumab on the developing human fetus are unknown. For this reason, and because other therapeutic agents used in this trial are known to be teratogenic, women of childbearing potential (WOCBP) receiving nivolumab must continue contraception for a period of 5 months after the last dose of nivolumab. Women who are not of childbearing potential (i.e., who are postmenopausal or surgically sterile) as well as azoospermic men do not require contraception.
- +5 more criteria
You may not qualify if:
- Patients who have received a liver, lung, heart, or pancreas transplant; or allogeneic stem cell transplant; or any kind of bone marrow transplant
- Patients unwilling or unable to undergo dialysis in the event of allograft failure
- Patients with prior evidence of human leukocyte antigen (HLA) or non-HLA donor-specific antibodies (DSA)
- Patients with a history of antibody- or cell-mediated allograft rejection within 3 months of study entry
- Potential trial participants should have recovered from clinically significant adverse events of their most recent therapy/intervention prior to enrollment
- Patients may have received prior anti-PD-(L)1 therapy; however, patients must not have any other checkpoint antibody targeting T-cell co-stimulation within 1 year of study enrollment. Prior history of adjuvant therapy is allowed if received over 1 year prior to enrollment. Prior receipt of oncolytic therapy (e.g., TVEC, RP1) is allowed
- Patients must not be receiving any other investigational agents
- Patients must not have a history of severe hypersensitivity reaction to any monoclonal antibody
- Patients must not have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to other agents used in the study
- Patients must not have uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or any other significant condition(s) that would make this protocol unreasonably hazardous
- Pregnant women are excluded from this study because nivolumab and ipilimumab have the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for AEs in nursing infants secondary to treatment of the mother, breastfeeding should be discontinued if the mother is treated with nivolumab or ipilimumab. These potential risks may also apply to other agents used in this study
- Patients with autoimmune disease that is active or might recur and affect vital organ function will be eligible only after consultation with the study PI. Guillain-Barre (GB) syndrome, bullous skin disease, Stevens Johnson syndrome, or toxic epidermal necrolysis will be excluded
- Patients must not have had evidence of active or acute diverticulitis, intra-abdominal abscess, GI obstruction and abdominal carcinomatosis which are known risk factors for bowel perforation should be evaluated for the potential need for additional treatment before coming on study. In addition, patients with a history of cardiac disease including coronary artery disease (CAD), myocardial infarction (MI), cardiomyopathy, arrhythmia, heart block, should have an evaluation by history pulmonary embolism (PE) and appropriate testing to allow evaluation of any events that may occur on study. These may include troponin, electrocardiogram (EKG), echocardiogram (ECHO) as clinically indicated and may include results already in the medical record if available
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (26)
UC San Diego Moores Cancer Center
La Jolla, California, 92093, United States
Keck Medicine of USC Koreatown
Los Angeles, California, 90020, United States
Los Angeles General Medical Center
Los Angeles, California, 90033, United States
USC / Norris Comprehensive Cancer Center
Los Angeles, California, 90033, United States
Sibley Memorial Hospital
Washington D.C., District of Columbia, 20016, United States
UM Sylvester Comprehensive Cancer Center at Aventura
Aventura, Florida, 33180, United States
UM Sylvester Comprehensive Cancer Center at Coral Gables
Coral Gables, Florida, 33146, United States
UM Sylvester Comprehensive Cancer Center at Deerfield Beach
Deerfield Beach, Florida, 33442, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, 33136, United States
UM Sylvester Comprehensive Cancer Center at Kendall
Miami, Florida, 33176, United States
University of Miami Sylvester Comprehensive Cancer Center at Sole Mia
North Miami, Florida, 33181, United States
UM Sylvester Comprehensive Cancer Center at Plantation
Plantation, Florida, 33324, United States
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, 30322, United States
Northwestern University
Chicago, Illinois, 60611, United States
Memorial Hospital East
Shiloh, Illinois, 62269, United States
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, 40536, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, 21287, United States
Siteman Cancer Center at Saint Peters Hospital
City of Saint Peters, Missouri, 63376, United States
Siteman Cancer Center at West County Hospital
Creve Coeur, Missouri, 63141, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Siteman Cancer Center-South County
St Louis, Missouri, 63129, United States
Siteman Cancer Center at Christian Hospital
St Louis, Missouri, 63136, United States
NYU Langone Hospital - Long Island
Mineola, New York, 11501, United States
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York, New York, 10016, United States
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, 15232, United States
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, 84112, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Evan J Lipson
JHU Sidney Kimmel Comprehensive Cancer Center LAO
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 8, 2023
First Posted
June 9, 2023
Study Start
July 24, 2024
Primary Completion (Estimated)
January 31, 2027
Study Completion (Estimated)
January 31, 2027
Last Updated
May 1, 2026
Record last verified: 2026-02
Data Sharing
- IPD Sharing
- Will share
NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.